Deficits in Acoustic Startle Reactivity and Auditory Temporal Processing after Traumatic Brain Injury.

Traumatic brain injury (TBI) exacts significant neurological and financial costs on patients and their families. In adult patients with moderate-to-severe TBI, central auditory impairments have been reported. These auditory impairments may interfere with language receptivity, as observed in children with developmental brain injury.

Proteoglycan 4 Reduces Neuroinflammation and Protects the Blood-Brain Barrier after Traumatic Brain Injury.

Neuroinflammation and dysfunction of the blood-brain barrier (BBB) are two prominent mechanisms of secondary injury in neurotrauma. It has been suggested that Toll-like receptors (TLRs) play important roles in initiating and propagating neuroinflammation resulting from traumatic brain injury (TBI), but potential beneficial effects of targeting these receptors in TBI have not been broadly studied. Here, we investigated the effect of targeting TLRs with proteoglycan 4 (PRG4) on post-traumatic neuroinflammation and BBB function.

The legacy of Malcolm Beverley Segal (1937-2019) on the science and fields concerned with choroid plexus and cerebrospinal fluid physiology.

This article highlights the scientific achievements, professional career, and personal interactions of Malcolm B. Segal who passed away in July this year. Born in 1937 in Goodmayes, Essex, UK, Segal rose to the Chairman position in the Division of Physiology at United Medical and Dental School of Guy's and St.

TrkB-enhancer facilitates functional recovery after traumatic brain injury.

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits.

The Involvement of Pial Microvessels in Leukocyte Invasion after Mild Traumatic Brain Injury.

The pathophysiological mechanisms underlying mild traumatic brain injury (mTBI) are not well understood, but likely involve neuroinflammation. Here the controlled cortical impact model of mTBI in rats was used to test this hypothesis. Mild TBI caused a rapid (within 6 h post-mTBI) upregulation of synthesis of TNF-α and IL-1β in the cerebral cortex and hippocampus, followed by an increase in production of neutrophil (CXCL1-3) and monocyte (CCL2) chemoattractants.

Circulating matrix metalloproteinases in children with diabetic ketoacidosis.

Background And Objective: Matrix metalloproteinases (MMPs) mediate blood-brain barrier dysfunction in inflammatory disease states. Our objective was to compare circulating MMPs in children with diabetic ketoacidosis (DKA) to children with type 1 diabetes mellitus without DKA.

Research Design And Methods: This was a prospective study performed at five tertiary-care pediatric hospitals.

A New Panel of Blood Biomarkers for the Diagnosis of Mild Traumatic Brain Injury/Concussion in Adults.

No routine tests currently exist to objectively diagnose mild traumatic brain injury (mTBI)/concussion. Previously reported biomarkers for mTBI represented proteins released from damaged neurons or glia. However, low levels of these proteins, and/or the complexity of assays used for their detection, limits implementation of these biomarkers in routine practice.

The quest for a better insight into physiology of fluids and barriers of the brain: the exemplary career of Joseph D. Fenstermacher.

In June 2014 Dr. Joseph D. Fenstermacher celebrated his 80th birthday, which was honored by the symposium held in New London, NH, USA.

The Brown University Traumatic Brain Injury Research Consortium and the Norman Prince Neurosciences Institute.

This article provides an overview of the Brown University Traumatic Brain Injury Research Consortium (TBIRC) and summarizes the multidisciplinary basic and clinical neuroscience work being conducted by investigators at Brown University and the affiliate hospitals in association with the Norman Prince Neurosciences Institute (NPNI).

Synergistic interactions between cytokines and AVP at the blood-CSF barrier result in increased chemokine production and augmented influx of leukocytes after brain injury.

Several lines of evidence indicate that the blood-cerebrospinal fluid barrier (BCSFB), which primarily resides in the choroid plexus (CP), plays a significant pathophysiological role not only in neuroinflammatory diseases, such as multiple sclerosis, but also in traumatic brain injury (TBI). Here we investigated how arginine vasopressin (AVP) regulates function of the BCSFB in the context of post-traumatic neuroinflammation. It has previously been shown that AVP exacerbates various forms of brain injury, but the mechanisms underlying this AVP action are poorly understood.

Blood-brain barrier pathophysiology in traumatic brain injury.

The blood-brain barrier (BBB) is formed by tightly connected cerebrovascular endothelial cells, but its normal function also depends on paracrine interactions between the brain endothelium and closely located glia. There is a growing consensus that brain injury, whether it is ischemic, hemorrhagic, or traumatic, leads to dysfunction of the BBB. Changes in BBB function observed after injury are thought to contribute to the loss of neural tissue and to affect the response to neuroprotective drugs.

Posttraumatic invasion of monocytes across the blood-cerebrospinal fluid barrier.

The invasion of inflammatory cells occurring after ischemic or traumatic brain injury (TBI) has a detrimental effect on neuronal survival and functional recovery after injury. We have recently demonstrated that not only the blood-brain barrier, but also the blood-cerebrospinal fluid (CSF) barrier (BCSFB), has a role in posttraumatic recruitment of neutrophils. Here, we show that TBI results in a rapid increase in synthesis and release into the CSF of a major chemoattractant for monocytes, CCL2, by the choroid plexus epithelium, a site of the BCSFB.

Emerging concepts in the pathophysiology of traumatic brain injury.

A complex set of molecular and functional reactions is set into motion by traumatic brain injury (TBI). New research that extends beyond pathological effects on neurons suggests a key role for the blood-brain barrier, neurovascular unit, arginine vasopressin, and neuroinflammation in the pathophysiology of TBI. The prevalence of molecular derangements in TBI holds promise for the identification and use of biomarkers to assess severity of injury, determine prognosis, and perhaps direct therapy.

Multiple sites of vasopressin synthesis in the injured brain.

Previous studies have indicated that the primary targets for vasopressin actions on the injured brain are the cerebrovascular endothelium and astrocytes, and that vasopressin amplifies the posttraumatic production of proinflammatory mediators. Here, the controlled cortical impact model of traumatic brain injury in rats was used to identify the sources of vasopressin in the injured brain. Injury increased vasopressin synthesis in the hypothalamus and cerebral cortex adjacent to the posttraumatic lesion.

Vasopressin amplifies the production of proinflammatory mediators in traumatic brain injury.

Arginine vasopressin (AVP) has previously been shown to promote disruption of the blood-brain barrier, exacerbate edema, and augment the loss of neural tissue in various forms and models of brain injury. However, the mechanisms underlying these AVP actions are not well understood. These mechanisms were studied in AVP-deficient Brattleboro rats (Avp(di/di)), and their parental Long-Evans strain, using a controlled cortical impact model of traumatic brain injury (TBI).

The role of the choroid plexus in neutrophil invasion after traumatic brain injury.

Traumatic brain injury (TBI) frequently results in neuroinflammation, which includes the invasion of neutrophils. After TBI, neutrophils infiltrate the choroid plexus (CP), a site of the blood-cerebrospinal fluid (CSF) barrier (BCSFB), and accumulate in the CSF space near the injury, from where these inflammatory cells may migrate to brain parenchyma. We have hypothesized that the CP functions as an entry point for neutrophils to invade the injured brain.

The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury.

Background: GPR125 belongs to the family of Adhesion G protein-coupled receptors (GPCRs). A single copy of GPR125 was found in many vertebrate genomes. We also identified a Drosophila sequence, DmCG15744, which shares a common ancestor with the entire Group III of Adhesion GPCRs, and also contains Ig, LRR and HBD domains which were observed in mammalian GPR125.

Expression of junctional proteins in choroid plexus epithelial cell lines: a comparative study.

Background: There is an increasing interest in using choroid plexus (CP) epithelial cell lines to study the properties of the blood-cerebrospinal fluid barrier (BCSFB). Currently, there are three major CP-derived cell lines available. Z310 and TR-CSFB3, two immortalized cell lines carrying the simian virus 40 large T-antigen gene, were derived from rat CP epithelium, whereas the CPC-2 cell line was derived from human CP carcinoma.

Traumatic brain injury results in a concomitant increase in neocortical expression of vasopressin and its V1a receptor.

Arginine vasopressin (AVP) has been shown to promote the disruption of the blood-brain barrier (BBB) and the formation of edema in various animal models of brain injury. However, the source(s) of this AVP have not been identified. Since the cerebral cortex was considerably affected in some of these brain injury models, we sought to determine if AVP was produced in the cerebral cortex, and, if so, whether or not this cortical AVP expression was up regulated after injury.

Chronic hypernatremia increases the expression of vasopressin and voltage-gated Na channels in the rat choroid plexus.

The choroid plexus (CP) epithelium is one of the extrahypothalamic sources of arginine vasopressin (AVP). However, it is unclear whether the regulation of choroidal AVP synthesis in response to pathophysiological stimuli, such as hyperosmotic stress, is similar to that observed in the hypothalamus. In the present study, rats chronically implanted with cisterna magna cannulas, enabling the collection of cerebrospinal fluid (CSF) in freely moving animals, were subjected to salt loading.

The choroid plexus-cerebrospinal fluid system: from development to aging.

The function of the cerebrospinal fluid (CSF) and the tissue that secretes it, the choroid plexus (CP), has traditionally been thought of as both providing physical protection to the brain through buoyancy and facilitating the removal of brain metabolites through the bulk drainage of CSF. More recent studies suggest, however, that the CP-CSF system plays a much more active role in the development, homeostasis, and repair of the central nervous system (CNS). The highly specialized choroidal tissue synthesizes trophic and angiogenic factors, chemorepellents, and carrier proteins, and is strategically positioned within the ventricular cavities to supply the CNS with these biologically active substances.

Shedding of tumor necrosis factor type 1 receptor after experimental spinal cord injury.

In a number of stress conditions, the biological effects of tumor necrosis factor-alpha (TNF-alpha), such as the induction of neuronal apoptosis, are presumably attenuated by the soluble fragments of TNF receptors (sTNFRs). Within 1 h after spinal cord injury, increased synthesis and/or secretion of TNF-alpha is detectable at the injury site. However, the shedding of ectodomains of TNFRs in the traumatized spinal cord has not yet been reported.

Increased expression of vasopressin v1a receptors after traumatic brain injury.

Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V1a receptors after traumatic brain injury (TBI) in rats.

Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injury.

The formation of edema after traumatic brain injury (TBI) is in part associated with the disruption of the blood-brain barrier. However, the molecular and cellular mechanisms underlying these phenomena have not been fully understood. One possible factor involved in edema formation is vascular endothelial growth factor (VEGF).

Expression of two membrane fusion proteins, synaptosome-associated protein of 25 kDa and vesicle-associated membrane protein, in choroid plexus epithelium.

In addition to being the major site of cerebrospinal fluid formation, the choroid plexus epithelium emerges as an important source of polypeptides in the brain. Physiologically regulated release of some polypeptides synthesized by the choroid plexus has been shown. The molecular mechanisms underlying this polypeptide secretion have not been characterized, however.